Border collie Jack passed away on February 28, 2022

[k9diabetes]

Re: Jack the project!

There is an interaction between his Ketaconazole and the MP - will have to see if that's true with the prednisone also - that suggests possibly using a smaller dose of the steroid.

[k9diabetes]

Re: Jack the project!

So anyone up for primer on prednisone vs. methylprednisolone?

Vet Section of Drugs.com
http://www.drugs.com/vet/depo-medrol.html

Exceeding prednisolone in anti-inflammatory potency and having even less tendency than prednisolone to induce sodium and water retention, methylprednisolone offers the advantage over older corticosteroids of affording equally satisfactory anti-inflammatory effect with the use of lower doses and with an enhanced split between anti-inflammatory and mineralocorticoid activities. Estimates of the relative potencies of methylprednisolone and prednisolone range from 1.13 to 2.1, with an average of 1.5. In anti-inflammatory activity, as measured by the granuloma pouch assay, methylprednisolone is twice as active as prednisolone. In mineralocorticoid activity (ie, the capacity to induce retention of sodium and water in the adrenalectomized rat) methylprednisolone is slightly less active than prednisolone. The duration of plasma steroid levels following rapid intravenous injection in intact dogs is appreciably longer for methylprednisolone than for prednisolone, the respective “half-life” value for the two steroids being 80.9 ± 7.5 minutes for methylprednisolone and 71.3 ± 1.7 minutes for prednisolone.

While the effect of parenterally administered DEPO-MEDROL is prolonged, it has the same metabolic and anti-inflammatory actions as orally administered methylprednisolone acetate.

http://www.drugs.com/vet/medrol.html

With therapeutically equivalent doses, the likelihood of occurrence of troublesome side effects is less with methylprednisolone than with prednisolone; moreover, side effects actually have been conspicuously absent during clinical trials with MEDROL Tablets in dogs and cats. However, methylprednisolone is similar to prednisolone in regard to kinds of side effects and metabolic alterations to be anticipated when treatment is intensive or prolonged. In animal patients with diabetes mellitus, use of methylprednisolone may be associated with an increase in the insulin requirement.

Negative nitrogen balance may occur, particularly in animals that require protracted maintenance therapy; measures to counteract persistent nitrogen loss include a high protein intake and the administration when indicated, of a suitable anabolic agent. Excessive loss of potassium, like excessive retention of sodium, is not likely to be induced by effective maintenance doses of MEDROL. However, these effects should be kept in mind and the usual regulatory measures employed as indicated. Ecchymotic manifestations, while not noted during the clinical evaluation in dogs and cats, may occur. If such reactions do occur and are serious, reduction in dosage or discontinuance of methylprednisolone therapy may be indicated. Concurrent use of daily oral supplements of ascorbic acid may be of value in helping to control ecchymotic tendencies.

The keystone of satisfactory therapeutic management with MEDROL Tablets, as with its steroid predecessors, is individualization of dosage in reference to the severity of the disease, the anticipated duration of steroid therapy, and the animal patient's threshold or tolerance for steroid excess. The prime objective of steroid therapy should be to achieve a satisfactory degree of control with a minimum effective daily dose.

Ecchymotic:
The passage of blood from ruptured blood vessels into subcutaneous tissue, marked by a purple discoloration of the skin.

As with other orally administered corticosteroids, the total daily dose of MEDROL should be given in equally divided doses.

Average total daily oral doses for dogs and cats:
5 to 15 lb body wt 2mg
15 to 40 lb body wt 2 to 4 mg
40 to 80 lb body wt 4 to 8 mg

Jack weighs about 54 pounds and is on 8 mg once daily, I suspect to try to reduce the toxic effect per the information found elsewhere that once daily dosing is less toxic.

[k9diabetes]

Re: Jack the project!

http://www.marvistavet.com/html/body_prednisone.html

Prednisone is activated by the patient's liver into Prednisolone.

http://www.petplace.com/drug-library...one/page1.aspx

Prednisone is rapidly converted in the liver to prednisolone. Except in cases of severe liver disease, the drugs are considered the same (equivalent).

[k9diabetes]

Re: Jack the project!

http://www.peteducation.com/article....+1461&aid=1422

Mineralocorticoids: Mineralocorticoids get their name from the fact that they have the responsibility of maintaining the levels of the minerals sodium and potassium in the body, and because they are produced by the cortex of the adrenal glands. Through their effect on sodium and potassium, as well as other actions, they conserve or maintain the body's concentration of water at a near constant level. Mineralocorticoids exert most of their effect on the kidneys, causing parts of these organs to selectively excrete excess potassium in the urine and at the same time conserve or retain sodium. These actions maintain the concentrations of these electrolytes within a very narrow range that is compatible with life. The use of the mineralocorticoids or their synthetically produced imitations in veterinary medicine is much less common than the other two forms of steroids.

Glucocorticoids: The previously mentioned cortisol belongs to the glucocorticoid group. The members of this group get their name because they affect glucose metabolism and are produced by the cortex section of the adrenal glands. The glucocorticoids are the predominant steroids used in veterinary medicine. These naturally occurring steroids cause proteins (e.g., muscles) and lipids (e.g., body fats) to be chemically broken down and converted into glucose. This is why the glucocorticoids are also referred to as the "catabolic" steroids. Catabolism means to break down large molecules into smaller ones. Additionally, the glucocorticoids also cause carbohydrates stored in the form of glycogen to be converted back to glucose and deposited into the circulating blood. There it is available to all the body's tissues. To break down the proteins or fats of the body may seem harmful to the animal, but remember that glucose is the main energy source for all of the body's activities. The vast majority of the glucose that the body utilizes comes directly from the diet or stored glycogen, but in emergency situations it can be derived from its own protein and lipids. It is generally thought that the glucocorticoids only cause this to occur to a significant degree during periods of exceptional need.

Glucocorticoids also suppress inflammatory processes within the body. A bruise, bee sting, bacterial infection, or arthritis are just a few examples of inflammation within a pet's body. Inflammation is specifically defined as an area of the body characterized by redness, swelling, heat, and pain, often with impaired function. The warmth and redness seen in these affected tissues comes from an increase in the number and size of blood vessels within the area. The swelling (edema) is caused by free fluid within the tissues and also the engorged blood vessels. All of these changes are brought on by physical trauma and/or irritants within the tissues. The pain is caused by the swelling, by harmful substances putting pressure on, or by stimulating the local nerve fibers. The loss of function can be caused by pain or the simple inability of the body to move or act correctly.

An example of the inflammatory action of glucocorticoids is in their use in an animal that has ruptured a disc between the vertebrae in its back. The swollen, herniated disc puts pressure on the spinal cord and other nerve fibers in the area. This is painful and the pressure on the spinal cord prevents nerve impulses from passing between the brain and the rear part of the body. The animal may be unable to walk or control its colon or bladder. Severe damage to the spinal cord can lead to total paralysis or death. Although surgery is required in a small portion of these cases to relieve the pressure on the spinal cord, most of these dogs can be successfully handled with rest and steroids. The steroids, and this case it is often dexamethasone, are able to remove the swelling and fluids within the disc and surrounding tissues, thereby removing the pressure from the spinal cord. This allows the nerve fibers within it to function correctly. Given time, the disc shrinks back down and the steroids are slowly discontinued. Remember, the steroids do not 'heal' the disc; they only reduce the swelling while it slowly returns to its normal size and shape.

Increased water consumption and increased urination: are two of the most common side effects of glucocorticoid usage. Although it can be quite disconcerting to the owner of a pet that lives predominately in the home, it is not by itself a serious problem. Glucocorticoids increase the activity of the glomeruli, which are the filtration units of the kidneys. This causes the animal to excrete higher levels of urine. The loss stimulates thirst in an attempt to replace lost fluids. These actions may increase water consumption and urination to the point that the animal can control neither one. Such signs can be observed within hours of initiating steroid therapy if the initial dosages were too high for the individual animal to tolerate. When long-acting injectable forms are used at excessive levels, increased water consumption and urination can continue for several weeks.

[k9diabetes]

Re: Jack the project!

The upshot I got from all of that is that Jack may need a smaller dose.

Natalie

[AlisonandMia]

Re: Jack the project!

I've just been looking into this methylprednisolone -v- prednisone thing. Everything seems to come up saying they are effectively the same thing in most cases. I think I remember reading somewhere in the dim and distant past that there can be a functional difference when the steroid is being aimed at liver inflammation but for most purposes such as asthma, muscular skeletal stuff etc. the two are interchangeable except that methylpred is a little bit more potent per mg - ie 10mg methylpred = 12.5mg pred so the dose needs to be adjusted accordingly. (See this very useful link: http://www.globalrph.com/steroid.cgi)

I believe that methylprednisolone is sometimes used as a local treatment - injected into a joint or whatever and when it is used that way I guess there would be less (or no significant) systemic effects such as PU/PD. So maybe this is what the vet was thinking of(?) - can't find anything about methylpred not causing PU/PD in animals when given systemically.

From what we see at K9Cushing's with dogs with naturally occurring Cushing's is that there is a fair bit of variation in the degree of PU/PD in response to high cortisol. Some just seem to be more effected that way than others and a few even seem to lack that symptom altogether (Kim's Haley was one that comes to mind). Looks like poor Jack is very sensitive to corticosteroids in that particular way - and he is far from alone in that. Strange thing is PU/PD is not usually a really troublesome side effect in humans on corticosteroids. I've known a fair few people who have taken steroids and none have ever commented on having to get up umpteen times a night etc.. Thank goodness dogs don't have the mood swings, tetchiness and even outright psychosis that people get though!

I guess the idea with Jack's condition was to hit it fairly hard with the steroids early on for a short period (around 3 - 5 days) to damp the inflammation down and then taper off from there. That is normally how steroids are used with inflammatory conditions and it is how may daughter takes them when she has a bad asthma flair up.

Alison

PS: Found this:

Common adverse side effects of methylprednisolone include vomiting, behavior modification, lethargy, increased water intake, increased frequency of urination, increased appetite and panting.

(http://www.petplace.com/drug-library...rol/page1.aspx)

[buddingartist]

Re: Jack the project!

Natalie, I really hesitated about posting this since you could run circles around me with your level of knowledge and comprehension of this technical material but I so feel for both you and Jack.

I have taken to do research on every med that is prescribed for Buddy as he has developed a pattern of reacting violently to the higher dosage recommended and it has screwed him up badly in the past. This problem is further compounded in Canada with kilo and pounds and the vet has made that mistakes a few times. Besides you got me curious

From what I understand the methyl has the potential of achieving the same results with lower dosage. I read a few articles on methylprednisone and prednisone and I don't know if you saw this article on the Pfizer site. (Medrol)

http://www.pfizerah.com/pahimages/pd...M_Detailer.pdf

If you can't open this PDF document from the link above
http://www.pfizerah.com/product_over...=EN&species=CN

Pages 9 and 10 are quite informative. Jack seems to be at the higher recommended dosage, and this reinforces that your instinct to reduce the dosage by half is dead on. It also reinforces that it should be administered equally twice a day to minimize toxicity.

I really hope things get better for both of you.

Louise

[k9diabetes]

Re: Jack the project!

It looks like much of what was on Drugs.com came from the Pfizer insert so we are on the same page Louise.

I have a call in to the neurologist to talk about what to do from here. Jack is due for another MP this morning but I will wait to give him anything to see if I can catch the neurologist first.

Jack's been on some level of prednisone, either as pred or as MP (two days were less than full doses), for 6 days now so it's possible that we could start to taper him off of it. And I'm hoping to do that at a lower dose than what we have been giving.

Natalie

[k9diabetes]

Re: Jack the project!

The one difference I see with the methyl-prednisolone is that the urinary effect seems to dissipate sooner after a dose is given. This afternoon, 22 hours after his last dose of it, he was able to go three hours between potty trips.

I wasn't able to reach the neurologist so I skipped his dose tonight and plan to start the every other day dosing process of tapering him off of it unless I hear different from the neurologist before tomorrow afternoon.

Only remaining question is whether to give him a whole tablet or half a tablet tomorrow.

Natalie

[k9diabetes]

Re: Jack the project!

I gave him half a tab with breakfast.

[buddingartist]

Re: Jack the project!

It's 7:30pm my time as I read this.

How's Jack doing on half a tab? Is mommy getting a bit of rest?

Louise

[k9diabetes]

Re: Jack the project!

It's about 9:30pm our time. I'd say his drinking is up some starting this afternoon but he seems to be able to go several hours - 2 to 3 hours maybe - in between trips. Last night I set alarms for every 2.25 hours and he did fine with that. I will probably try something similar tonight unless his drinking and peeing really winds up between now and then.

He had a really fun walk at lunch time today and seemed to do pretty well out there. Now he's subdued... he always seems a little punky after getting the pred. I'm hoping he can shake it faster with the smaller dose.

Natalie

[buddingartist]

Re: Jack the project!

I guess if he had a <fun walk<, the meds are starting to alleviate the pain which would be the good news I guess.

Every 2 1/2 hours All that rest that you got

Hope it continues to improve

Louise

[k9diabetes]

Re: Jack the project!

Jack had his second 1/2 tab of methyl-prednisolone yesterday about 11am. Around 8 p.m., his urinating started increasing. We tried to go 2.5 hours between potty trips last night but that was too long and he leaked some before he woke up to ask to go out. So we cut the timing back to every 1.5 hours. He needed trips that frequently until about 3 a.m., after which he was able to hold it longer, more like three hours. And he seems pretty normal today.

So the frequent urination still occurs on 4mg but doesn't last as long.

We are working him off of the methyl-prednisolone with every-other-day dosing through next week.

I don't think we could stand to do even half a tab every day for a week so prednisone just doesn't seem like a viable option for him in the future unless we are desperate.

Monday night... a full 8 hours of uninterrupted sleep. That was nice. Hoping for the same tonight and then it's another pred dose on Thursday.

Natalie

[Patty]

Re: Jack the project!

How's his pain level seem to be Natalie?